Autosomal polycystic kidney disease (ADPKD) is the most common genetic form of kidney failure, reflecting unmet needs in management. Prescription of the only approved treatment (tolvaptan) is limited ...to persons with rapidly progressing ADPKD. Rapid progression may be diagnosed by assessing glomerular filtration rate (GFR) decline, usually estimated (eGFR) from equations based on serum creatinine (eGFRcr) or cystatin-C (eGFRcys). We have assessed the concordance between eGFR decline and identification of rapid progression (rapid eGFR loss), and measured GFR (mGFR) declines (rapid mGFR loss) using iohexol clearance in 140 adults with ADPKD with ≥3 mGFR and eGFRcr assessments, of which 97 also had eGFRcys assessments. The agreement between mGFR and eGFR decline was poor: mean concordance correlation coefficients (CCCs) between the method declines were low (0.661, range 0.628 to 0.713), and Bland and Altman limits of agreement between eGFR and mGFR declines were wide. CCC was lower for eGFRcys. From a practical point of view, creatinine-based formulas failed to detect rapid mGFR loss (-3 mL/min/y or faster) in around 37% of the cases. Moreover, formulas falsely indicated around 40% of the cases with moderate or stable decline as rapid progressors. The reliability of formulas in detecting real mGFR decline was lower in the non-rapid-progressors group with respect to that in rapid-progressor patients. The performance of eGFRcys and eGFRcr-cys equations was even worse. In conclusion, eGFR decline may misrepresent mGFR decline in ADPKD in a significant percentage of patients, potentially misclassifying them as progressors or non-progressors and impacting decisions of initiation of tolvaptan therapy.
The atypical hemolytic-uremic syndrome (aHUS) is characterized by the triad of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The aHUS is related to complement dysregulation; ...since the approval of eculizumab for this entity (a monoclonal antibody that inhibits C5 activation and blocks the formation of the membrane attack complex) the prognosis has improved. The recurrence of aHUS after kidney transplantation is frequent and implies loss of the graft in a high percentage of cases. Eculizumab prophylaxis to prevent recurrence has allowed successful kidney transplantation in this group of patients. We present a series of kidney transplant patients with chronic kidney disease secondary to aHUS and the use of eculizumab for prevention of recurrence.
ABSTRACT
Background
Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients ...(DKTRs) is limited.
Methods
This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment.
Results
Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio OR 7.90 confidence interval (CI) 3.63–17.21} and female sex OR 2.46 (CI 1.19–5.03). In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight −2.22 kg (95% CI −2.79 to −1.65), blood pressure, fasting glycaemia, haemoglobin A1c −0.36% (95% CI −0.51 to −0.21), serum uric acid −0.44 mg/dl (95% CI −0.60 to −0.28) and urinary protein:creatinine ratio, while serum magnesium +0.15 mg/dl (95% CI 0.11–0.18) and haemoglobin levels rose +0.44 g/dl (95% CI 0.28–0.58. These outcomes persisted in participants followed over 12 months of treatment.
Conclusions
SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.
Lay Summary
Experience with sodium–glucose cotransporter-2 inhibitor (SGLT2i) treatment in diabetic kidney transplant recipients (DKTRs) is limited, as these agents may increase the risk of kidney graft dysfunction and urinary tract infection (UTI). Recently, however, these drugs have shown clear nephroprotective and cardioprotective effects in non-transplanted individuals with diabetes. The objective of this multicentre study was to describe our experience with SGLT2i treatment in DKTRs.
Treatment was effective in controlling glycemia and had the additional benefits of improving weight, blood pressure, anaemia, proteinuria and serum levels of magnesium and uric acid. However, the frequency of UTI was greater than that reported for non-transplanted diabetic individuals. Previous UTIs and female sex were identified as risk factors for developing a UTI.
The findings of this study suggest that as with non-transplanted diabetics, DKTRs will benefit from SGLT2i treatment, although female patients and those with a history of UTI need to be closely monitored.
Graphical Abstract
Graphical Abstract
Data on the combined associations of albuminuria and estimated glomerular filtration rate (eGFR) with renal transplant outcomes are limited. Our objective was to explore how renal transplant outcomes ...could be predicted by a combined variable of early low-grade albuminuria and allograft dysfunction.
We studied a cohort of adult deceased-donor kidney transplant recipients who were subdivided into four groups according to median albuminuria (100 mg/day, interquartile range, 0-470 mg/day) and median eGFR (60 mL/min/1.73 m(2); interquartile range, 30-73 mL/min/1.73 m(2)) at third month posttransplantation as follows: group I (albuminuria <100 and eGFR >60, n=238); group II (albuminuria ≥100 and eGFR >60, n=151); group III (albuminuria <100 and eGFR ≤60; n=167); and group IV (albuminuria ≥100 and eGFR ≤60, n=228).
Death-censored graft survival was significantly lower in group IV compared with the rest (P<0.0001). Multivariate Cox regression analysis using fixed and time-dependent covariates showed that the combination of low-grade albuminuria and lower eGFR was associated with graft failure (hazard ratio, 2.2, 95% confidence interval, 1.3-3.7; P=0.003). Likewise, but to a lesser extent, the risk of mortality was increased for group IV (hazard ratio, 1.7, 95% confidence interval, 1.01-2.8; P=0.042).
Early association of low-grade albuminuria and allograft dysfunction represents an important risk factor of graft failure and mortality. This additive effect should be considered to identify individuals at risk for adverse kidney transplantation outcomes.
Patients with chronic kidney disease (CKD) have a high symptoms burden that is related to a poor health-related quality of life (HRQoL) and high costs of care. Validated instruments may be useful for ...assessing the symptoms and monitoring outcomes in these patients. The Palliative care Outcome Scale-Symptoms Renal (POS-S Renal) is a patient-reported outcome measure for assessing symptoms in CKD stage 4-5. This study is the first cross-cultural adaptation and psychometric analysis of this clinical tool. The purpose of this study is to carry out a cross-cultural adaptation of the POS-S Renal for Spanish-speaking patients, and to perform an analysis of the psychometric properties of this questionnaire.
The English version of the POS-S Renal was culturally adapted and translated into Spanish using a double forward and backward method. An expert panel evaluated the content validity. The questionnaire was pilot-tested in 30 patients. A total of 200 patients with CKD stage 4-5 filled in a modified Spanish version of the POS-S Renal and the MSAS-SF. Statistical analysis to evaluate the psychometric properties of the questionnaire was carried out.
The content validity index (CVI) was 0.97, which indicated that the content of the instrument is an adequate reflection of the symptoms in advanced CKD (ACKD). The factor analysis indicated a two-factor solution explaining 35.05% of total variance. The confirmatory factor analysis (CFA) demonstrated that the two factor model was well supported (comparative fit index = 0.98, root mean square error of approximation = 0.068). This assessment tool demonstrated a satisfactory test-retest reliability (r = 0.909 to factor 1, r = 0.695 to factor 2, r = 0.887 to total score), good internal consistency to factor 1 (α = 0.78) and moderate internal consistency to factor 2 (α = 0.56). Concurrent criterion-related validity with MSAS-SF was also demonstrated, with r = 0.860, which indicated a high degree of correlation with a validated instrument that has been used in patients with ACKD.
The Spanish modified version of the POS-S Renal is a reliable and valid instrument that can be used to assess symptoms in Spanish patients with CKD stage 4-5.
Background
Post-transplant diabetes mellitus (PTDM) beyond 12 months (late PTDM) is a severe complication after renal transplantation. Late PTDM develops mostly in subjects with prediabetes. Although ...exercise may have a potential role in preventing late PTDM, there are no previous data on the effect of exercise in patients with prediabetes.
Material and Methods
The design was a 12-month exploratory study to test the capacity of exercise in reverting prediabetes in order to prevent late-PTDM. The outcome was the reversibility of prediabetes, assessed every 3 months with oral glucose tolerance tests (OGTT). The protocol included an incremental plan of aerobic and/or strength training as well as an active plan for promoting adherence (telephone calls, digital technology, and visits). A priori, a sample size cannot be calculated which makes this an exploratory analysis. Based on previous studies, the spontaneous reversibility of prediabetes was 30% and the reversibility induced by exercise will account for another 30%, a total reversibility of 60% (
p
value < 0.05, assuming a potency of 85%). Ad interim analysis was performed during follow-up to test the certainty of this sample calculation. Patients beyond 12 months after renal transplantation with prediabetes were included.
Results
The study was interrupted early due to efficacy after the evaluation of the follow-up of 27 patients. At the end of follow-up, 16 (60%) patients reverted to normal glucose levels at fasting (from 102.13 mg/dL ± 11 to 86.75 ± 6.9,
p
= 0.006) and at 120 min after the OGTTs (154.44 mg/dL ± 30 to 113.0 ± 13.1,
p
= 0.002) and 11 patients had persistent prediabetes (40%). Also, insulin sensitivity improved with the reversibility of prediabetes, compared to those with persistent prediabetes: 0.09 0.08–0.11 versus 0.04 0.01–0.07,
p
= 0.001 (Stumvoll index). Most needed at least one increment in the prescription of exercise and compliance. Finally, measures aimed at the improvement of compliance were successful in 22 (80%) patients.
Conclusion
Exercise training was effective to improve glucose metabolism in renal transplant patients with prediabetes. Exercise prescription must be conducted considering both the clinical characteristics of the patients and pre-defined strategy to promote adherence. The trial registration number of the study was NCT04489043.
Key Points
PTDM is a risk factor for major complications: cardiovascular diseases, infections, and renal cell cancer. Strategies to prevent PTDM are limited.
Exercise training is an effective alternative to improve glucose metabolism in renal transplant patients. Thus, exercise can be considered, together with diet and medications, as a tool to treat and prevent these complications.
A pre-defined strategy to improve compliance must be considered simultaneously with exercise prescription.
Abstract
Background
Subclinical inflammation, including borderline lesions (BL), is very common (30–40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to ...interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function.
Methods
The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression.
Discussion
This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL.
Trial registration
clinicaltrials.gov
: NCT04936282. Registered June 23, 2021,
https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1
. Protocol Version 2 of 21 January 2022. Sponsor: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org.
The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established.
We performed a cross-sectional study in 727 ...stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally.
Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I–III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01–1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6–6.3); in females, age (OR 1.07; 95% CI: 1.03–1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043–1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters.
Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.
La relación entre las alteraciones del metabolismo mineral, las fracturas óseas y las calcificaciones vasculares en receptores de un trasplante renal no han sido establecidas.
Realizamos un estudio transversal en 727 receptores estables procedentes de 28 centros de trasplante españoles. Se determinaron de manera centralizada los parámetros del metabolismo mineral; también se centralizó la semicuantificación de las fracturas vertebrales y de las calcificaciones de la aorta abdominal.
La deficiencia de vitamina D (25OHD3 < 15ng/ml) fue más frecuente en mujeres y en los estadios CKD-T I-III (29,6 vs. 44,4%; p=0,003). La relación inversa y significativa observada entre los niveles de 25OHD3 y PTH fue modificada por el género de tal manera que la pendiente fue mayor en las mujeres que en los hombres (p=0,01). Un 15% de los receptores mostró alguna fractura vertebral (VFx) con un grado de deformidad ≥2. Los factores relacionados con la VFx diferían en función del género: en los hombres, la edad (OR: 1,04; IC 95%: 1,01-1,06) y el tratamiento con CsA (OR: 3,2; IC 95: 1,6-6,3); en las mujeres la edad (OR: 1,07; IC 95%: 1,03-1,12) y los niveles de PTH (OR per 100pg/ml increase: 1,27; IC 95%: 1,043-1,542). Las calcificaciones de la aorta abdominal fueron comunes (67,2%) y se relacionaron con los factores de riesgo clásicos, pero no con los parámetros del metabolismo mineral.
La deficiencia de vitamina D es más frecuente en las mujeres receptoras de un trasplante renal y en los estadios más tempranos de la CKD-T, y es un factor que contribuye al desarrollo de hiperparatiroidismo secundario. Las VFx prevalentes están relacionadas con unos niveles más elevados de PTH solamente en las mujeres.
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